Obesity, diabetes and heart disease are characterized by resistance to insulin as a glucoregulatory hormone. African Americans, particularly African American women suffer disproportionately from these three conditions. We believe that sex differences in sensitivity to insulin?s ability to suppress lipolysis contribute to the accelerated development of obesity, diabetes and heart disease in African American women. The hypothesis of this research is that African American men are resistant to insulin as a glucoregulatory hormone and resistant to insulin as a fat regulatory hormone. In contrast, African American women are resistant to insulin as a glucoregulatory hormone but sensitive to insulin as a fat regulatory hormone. The frequently sampled intravenous glucose tolerance test is used to measure insulin?s action as a glucoregulatory hormone. Unfortunately there is no index of insulin?s action as a fat regulatory hormone. Hence we are working on the development of this index by obtaining free fatty acids during the frequently sampled glucose tolerance test. Our goal is be able to do one test to obtain information about both actions of insulin. However, the development of an index of free fatty acid sensitivity to insulin during the frequently sampled intravenous glucose tolerance test involves sophisticated mathematical modeling and will need to be validated. As we work towards developing this index, we have studied sex differences in body fat content and distribution in African Americans. The distribution of body fat has a major impact on the interaction between insulin and body fat. We determined using serial slice computerized tomographic scans and dual X-ray absorptiometry (DXA) that there are sex differences in central body fat distribution in African Americans. These findings were published in the American Journal of Clinical Nutrition in November 2002. In addition, we have found that beta cell secretion of insulin is impaired in obese glucose intolerant African American women and this work was published in Diabetes Care in 2001. Now we are concentrating on sex differences in the free fatty acid profile during the frequently sampled intravenous glucose tolerance test. It is the intent that this free fatty acid work through the complicated process of modeling will lead to the development of an index of free fatty acid sensitivity to insulin. The development of this index is required so the research hypotheses can be fully tested. Further we are investigating the ability of insulin and lipid related variables to predict heart disease risk in African Americans.